2,485 research outputs found

    Identification of a novel regulatory mechanism for the disease associated protein, uPAR

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    Expression quantitative trait loci (eQTLs), as determined through a series of statistical association studies collectively known as genome-wide association (GWA) studies, have provided us with a hypothesis free approach for the investigation into regulatory loci for disease and disease-associated proteins. This has led to the identification of multiple novel gene-disease interactions, especially in the field of respiratory medicine. This review describes the case study of a GWA approach in order to identify eQTLs for the soluble form of the urokinase plasminogen activator receptor (uPAR), a protein associated with obstructive respiratory disease. Molecular and cellular investigations based on the eQTLs identified for this GWA study has led to the identification of a novel regulatory mechanism with implications in the disease processes with which this protein is associated. This highlights the potential of eQTLs defined associations in the identification of novel mechanisms, with implications in disease.peer-reviewe

    Symbolic Computation of Polynomial Conserved Densities, Generalized Symmetries, and Recursion Operators for Nonlinear Differential-Difference Equations

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    Algorithms for the symbolic computation of polynomial conserved densities, fluxes, generalized symmetries, and recursion operators for systems of nonlinear differential-difference equations are presented. In the algorithms we use discrete versions of the Fréchet and variational derivatives, as well as discrete Euler and homotopy operators. The algorithms are illustrated for prototypical nonlinear polynomial lattices, including the Kac-van Moerbeke (Volterra) and Toda lattices. Results are shown for the modified Volterra and Ablowitz-Ladik lattices

    Assessing Future Flood Risk and Developing Integrated Flood Risk Management Strategies: A Case Study from the UK Climate Change Risk Assessment

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    As Earth’s climate changes, individual nations must develop adaptation plans to respond to increasing or new climate risks. This study focuses on changing flood risk in England, UK, and examines the policy framework and actions that underpin England’s adaptation from a flood risk management (FRM) perspective. Specifically, the flood risk projections that fed into the UK’s Climate Change Risk Assessment were analysed alongside newly developed FRM adaptation portfolios that modified the flood risk projections to identify the potential of different measures to reduce Expected Annual Damages (EAD). The key findings indicate that: the range of EAD for all flood sources combined is projected to increase by 18–160% by the 2080s depending on the climate change, population growth and adaptation assumptions applied; adopting an enhanced adaptation approach presents an opportunity to manage much of the climate driven change in flood risk, particularly from river flooding; EAD from coastal flood risk shows the greatest increase relative to present day; and surface water flooding will become an increasingly more significant source of flood risk. Interpretation of the results in the context of the policy framework shows how greater coordination and integration of risk managers and interventions is required to improve adaptation planning

    Determining the predictive capability of a Clinical Assessment Scoring Chart to differentiate severity of the clinical consequences of neonatal calf diarrhea relative to gold-standard blood gas analysis

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    peer-reviewedNeonatal calf diarrhea (NCD) is a major problem to calf health worldwide, in terms of both morbidity and mortality. A five-point ordinal scale clinical assessment scoring (CAS) chart was utilized to assess calves suffering from NCD-related clinical abnormalities (acidosis and dehydration) on commercial farms. The objective of this research was to determine the predictive capability of this CAS chart against gold standard blood gas parameters, designed to assist farmers in the accurate assessment of the clinical consequences of NCD. A total of 443 diarrheic and non-diarrheic calves were enrolled in the study. The CAS chart rated a calf’s health from no clinical signs to varying degrees of clinical severity on a 0 (clinically normal) to 4 (grave) scale, based on clinical indicators including calf demeanour, ear position, mobility, suckle reflex, desire-to-feed, and enophthalmos. Blood gas analysis was conducted for individual calves, consisting of pH, base excess, Na+, K+, Ca2+, Cl−, glucose, total hemoglobin, bicarbonate, anion gap, and strong ion difference. Statistical evaluation was performed by comparison of the CAS score with blood gas profiles using ordinal logistic regression and a non-parametric estimation of the Receiver Operating Characteristics (ROC). The ROC analysis indicated that the CAS chart had acceptable specificity (>95%) with low sensitivity (80%) but had reduced accuracy in differentiating mild and moderate cases (peak estimations >50%). The chart, as presented, provides a simple tool to differentiate clinically normal from calves suffering the consequences of diarrhea, but fails to accurately differentiate severity for NCD related acidosis and dehydration. Further efforts are required to enhance the sensitivity and differential diagnostic value of this type of chart

    Flood vulnerability, risk and social disadvantage: current and future patterns in the UK

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    Present day and future social vulnerability, flood risk and disadvantage across the UK are explored using the UK Future Flood Explorer. In doing so, new indices of neighbourhood flood vulnerability and social flood risk are introduced and used to provide a quantitative comparison of the flood risks faced by more and less socially vulnerable neighbourhoods. The results show the concentrated nature of geographic flood disadvantage. For example, ten local authorities account for fifty percent of the most socially vulnerable people that live in flood prone areas. The results also highlight the systematic nature of flood disadvantage. For example, flood risks are higher in socially vulnerable communities than elsewhere; this is shown to be particularly the case in coastal areas, economically struggling cities and dispersed rural communities. Results from a re-analysis of the Environment Agency’s Long-Term Investment Scenarios (for England) suggests a long-term economic case for improving the protection afforded to the most socially vulnerable communities; a finding that reinforces the need to develop a better understanding of flood risk in socially vulnerable communities if flood risk management efforts are to deliver fair outcomes. In response to these findings the paper advocates an approach to flood risk management that emphasizes Rawlsian principles of preferentially targeting risk reduction for the most socially vulnerable and avoids a process of prioritisation based upon strict utilitarian or purely egalitarian principles

    Effects of High-Speed Power Training on Muscle Performance and Braking Speed in Older Adults

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    We examined whether high-speed power training (HSPT) improved muscle performance and braking speed using a driving simulator. 72 older adults (22 m, 50 f; age = 70.6 ± 7.3 yrs) were randomized to HSPT at 40% one-repetition maximum (1RM) (HSPT: n = 25; 3 sets of 12–14 repetitions), slow-speed strength training at 80%1RM (SSST: n = 25; 3 sets of 8–10 repetitions), or control (CON: n = 22; stretching) 3 times/week for 12 weeks. Leg press and knee extension peak power, peak power velocity, peak power force/torque, and braking speed were obtained at baseline and 12 weeks. HSPT increased peak power and peak power velocity across a range of external resistances (40–90% 1RM; P < 0.05) and improved braking speed (P < 0.05). Work was similar between groups, but perceived exertion was lower in HSPT (P < 0.05). Thus, the less strenuous HSPT exerted a broader training effect and improved braking speed compared to SSST

    Rumen fluke in Irish sheep: prevalence, risk factors and molecular identification of two paramphistome species

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    peer-reviewedBackground Rumen flukes are trematode parasites found globally; in tropical and sub-tropical climates, infection can result in paramphistomosis, which can have a deleterious impact on livestock. In Europe, rumen fluke is not regarded as a clinically significant parasite, recently however, the prevalence of rumen fluke has sharply increased and several outbreaks of clinical paramphistomosis have been reported. Gaining a better understanding of rumen fluke transmission and identification of risk factors is crucial to improve the control of this parasitic disease. In this regard, a national prevalence study of rumen fluke infection and an investigation of associated risk factors were conducted in Irish sheep flocks between November 2014 and January 2015. In addition, a molecular identification of the rumen fluke species present in Ireland was carried out using an isolation method of individual eggs from faecal material coupled with a PCR. After the DNA extraction of 54 individual eggs, the nuclear fragment ITS-2 was amplified and sequenced using the same primers. Results An apparent herd prevalence of 77.3 % was determined. Several risk factors were identified including type of pasture grazed, regional variation, and sharing of the paddocks with other livestock species. A novel relationship between the Suffolk breed and higher FEC was reported for the first time. The predominant rumen fluke species found was C. daubneyi. Nevertheless, P. leydeni was unexpectedly identified infecting sheep in Ireland for the first time. Conclusions An exceptionally high prevalence of rumen fluke among Irish sheep flocks has been highlighted in this study and a more thorough investigation is necessary to analyse its economic impact. The isolation of individual eggs coupled with the PCR technique used here has proven a reliable tool for discrimination of Paramphistomum spp. This technique may facilitate forthcoming studies of the effects of paramphistomosis on livestock production. The most noteworthy finding was the identification of P. leydeni affecting sheep in Ireland, however further studies are required to clarify its implications. Also, a significant relationship between Suffolk breed and a heavier infection was found, which can be used as a starting point for future research on control strategies of rumen fluke infection.This study was funded by Irish Department of Agriculture, Food and the Marine research stimulus funding; project reference 13/ S/405

    Investigation of Graded La2NiO4+ Cathodes to Improve SOFC Electrochemical Performance

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    Mixed ionic and electronic conducting MIEC oxides are promising materials for use as cathodes in solid oxide fuel cells SOFCs due to their enhanced electrocatalytic activity compared with electronic conducting oxides. In this paper, the MIEC oxide La2NiO4+ was prepared by the sol-gel route. Graded cathodes were deposited onto yttria-stabilized zirconia YSZ pellets by dip-coating, and electrochemical impedance spectroscopy studies were performed to characterize the symmetrical cell performance. By adapting the slurries, cathode layers with different porosities and thicknesses were obtained. A ceria gadolinium oxide CGO barrier layer was introduced, avoiding insulating La2Zr2O7 phase formation and thus reducing resistance polarization of the cathode. A systematic correlation between microstructure, composition, and electrochemical performance of these cathodes has been performed. An improvement of the electrochemical performance has been demonstrated, and a reduction in the area specific resistance ASR by a factor of 4.5 has been achieved with a compact interlayer of La2NiO4+ between the dense electrolyte and the porous La2NiO4+ cathode layer. The lowest observed ASR of 0.11 cm2 at 800°C was obtained from a symmetrical cell composed of a YSZ electrolyte, a CGO interlayer, an intermediate compact La2NiO4+ layer, a porous La2NiO4+ electrode layer, and a current collection layer of platinum paste

    Operating Interaction and Teleprogramming for Subsea Manipulation

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    The teleprogramming paradigm has been proposed as a means to efficiently perform teleoperation in the subsea environment via an acoustical link. In such a system the effects of both limited bandwidth channels and delayed communications are overcome by transmitting not Cartesian or joint level information but rather symbolic, error-tolerant, program instructions to the remote site. The operator interacts with a virtual reality of the remote site which provides immediate visual and kinesthetic feedback. The uncertainty in this model can be reduced based on information received from the slave manipulator\u27s tactile contact with the environment. It is suggested that the current state of the model be made available to the operator via a graphical display which shows not only the position of objects at the remote site but also, through the use of color clues, the uncertainty associated with those positions. The provision of uncertainty information is important since it allows the operator to compromise between speed and accuracy. An additional operator aid, which we term synthetic fixturing, is proposed. Synthetic fixtures provide the operator of the teleprogramming system with the teleoperation equivalent of the snap commands common in computer aided design programs. By guiding the position and/or orientation of the master manipulator toward specific points, lines or planes the system is able to increase both the speed and precision with which the operator can control the slave arm without requiring sophisticated hardware
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